Our team is focused on basic and clinical research to better understand BPDCN, identify molecular targets, and improve outcomes. Findings include:
- All BPDCN cells overexpress CD123 (interleukin-3 receptor), a cell-surface protein. The BPDCN Center was a leader of the national clinical trial of the targeted immunotoxin tagraxofusp (also known as Elzonris or SL-401), a novel agent that targets the IL-3 receptor (CD123). This led to approval of tagraxofusp as the first drug specifically approved for BPDCN. A follow-up trial evaluated the long-term use and benefits of tagraxofusp for patients with BPDCN.
- In the laboratory, we have learned how BPDCN becomes resistant to tagraxofusp. This led to a new clinical trial testing the combination of tagraxofusp with azacitidine, a therapy already used in patients with other types of leukemia. We’ve outlined our approach to the use of tagraxofusp and discussed open questions in the treatment of BPDCN.
- By studying the characteristics of patients' BPDCN and the treatment received, we have defined factors associated with survival and identified new chemotherapy and targeted therapies that might be active in the disease.
- Researchers in the lab of Andrew Lane, MD, PhD, recently discovered that BPDCN is highly and uniquely dependent on the BCL-2 protein for survival. BCL-2 is a "pro-survival" protein that enables cancer cells to escape the "pro-death" signals that normally command abnormal cells to self-destruct through apoptosis, a natural quality-control process in the body.
- Dr. Lane co-authored major guidelines on treatment of BPDCN and co-led the formation of the North American BPDCN Consortium (NABC), which defines the current standard of care and future areas of need in BPDCN.
- Researchers confirmed that BPDCN is very sensitive to venetoclax, a BCL2 inhibitor developed at Dana-Farber. Two patients in a pilot study with relapsed disease responded to venetoclax. This research was reported in Cancer Discovery. A clinical trial is currently underway to evaluate venetoclax and azacitidine in BPDCN patients.
- Research from Dr. Lane’s lab led to the discovery that the reason why BPDCN is more common in males than females (~4:1 ratio) may be related to specific mutations on the X chromosome associated with the disease. Additional new findings were reported in Cancer Discovery.
- A research study from Dr. Lane and his colleagues found that ultraviolet radiation from the sun can cause genetic mutations in the tumors in the skin – and in leukemia tissue from blood and bone marrow. This research adds to the understanding of how BPDCN develops, helping to advance new treatments for the disease. These results also could have insights on how other cancers develop, specifically those involving blood or lymph cells. This research was reported in Nature, followed by a retrospective study in Blood Advances.
- Researchers developed a prognostic model for overall survival using a machine learning algorithm, including clinical, pathological, molecular and therapeutic data.